TreatmentUpdate 73 - Volume 8, No 9; November 1996
Sean Hosein

Some people with HIV/AIDS (PHAs) are also infected with the hepatitis B virus (HBV). Continuous, low-level infection of the liver by HBV can severely damage that organ, destroying it and even causing liver cancer. Interferon-alpha, a chemical made by the immune system, helps cells resist attack by certain viruses and has also been used to treat people with hepatitis B and HIV infections. Treatment of HBV with interferon-alpha does not bring the infection under control in most PHAs. The anti-HIV drug 3TC (lamivudine, Epivir ) also has anti-HBV activity. When 3TC was tested in people who had HBV, but not HIV infection, it suppressed production of HBV. We now report results from a study in France where PHAs who were also infected with HBV received 3TC to treat HBV.

Study details

Doctors recruited 40 volunteers or subjects of which 39 were male and 1 female for this study. After the experiment ended, researchers reviewed their data and found that the subjects could be divided into two groups depending on the level of HBV in their blood at the start of the study. Thus, 30 subjects had high levels of HBV (more than 5 pg/ml) and 10 others had low levels of HBV (less than 5 pg/ml). At first, the doctors gave some subjects 3TC 600 mg/day. Later this was reduced to 300 mg/day, which is the dose all subjects eventually used. Doctors monitored the subjects for 12 months while they took 3TC.

Results -- high HBV levels

* HBV levels

Twenty-six of 27 subjects in the group who used 3TC for 12 months had levels of HBV fall below 5 pg/ml. In six of these subjects who had used interferon-alpha before entering this study, HBV infection had been brought under control.

* Liver enzymes

Measuring the levels of liver enzymes in the blood is one way to monitor damage to the liver. Higher-than-normal levels of those enzymes occur when the liver is damaged by viruses or drugs. On average, the level of liver enzymes fell while subjects received 3TC. This decrease was statistically significant, that is, due to use of 3TC and not chance.

* CD4+ cells

The average CD4+ cell count at the start of the study in this group was 113 cells. This did not change during therapy.

Results -- low HBV level group

Technicians could not detect HBV in the blood of these subjects at the 6th and 12th months of the study. Levels of CD4+ cells and liver enzymes did not change during the 12 months subjects were in the study. A reduction of the dose of 3TC from 600 mg/day to 300 mg/day did not appear to affect recovery from HBV infection in either study group.

Toxicity and withdrawal from the study

Three subjects "dropped out of the study," one because of "frequent vomiting....and [stomach pain]." This subject had high levels of the enzyme amylase in his/her blood, while another subject left the study because of "personal reasons". Two subjects died because of complications due to Kaposi's sarcoma and a third died from an overwhelming bacterial infection. The researchers were unable to detect any liver damage caused by 3TC.

Interpretation

Use of 3TC was able to reduce production of HBV in 86% of subjects "as early as the [second] month of [the study]." After taking 3TC for 6 months, HBV could not be detected in blood samples taken from 96% of subjects. The anti-HBV activity of 3TC is greater than that seen when interferon-alpha is used. It is important to note that use of 3TC was able to suppress HBV infection but not cure it. It is likely that people infected with HIV whose immune systems are unable to control this infection will need longer courses of 3TC, lasting more than one year. The doctors who conducted the study do not recommend the use of 3TC in PHAs who have HBV infection. Before doing so, they would like to see results from larger studies confirming the results in this study. The doctors also want to monitor subjects after they have stopped using 3TC to find out if HBV infection is reactivated. Nonetheless, some PHAs with chronic HBV infection may find 3TC useful.

REFERENCES:

1. Benhamou Y, Katlama C, Lunel F, et al. Effects of lamivudine on replication of hepatitis B virus in HIV-infected men. Annals of Internal Medicine 1996;125(9):705-712.

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Copyright © 1996 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca